FDA Approves Ozanimod for Adults with Ulcerative Colitis

The US Food and Drug Administration (FDA) has approved ozanimod (Zeposia) 0.92 mg, an oral agent that selectively targets sphingosine-1-phosphate receptor subtypes 1 and 5, for adult patients with moderately to severely active ulcerative colitis.

The approval, awarded to Bristol Myers Squibb, was based on the data from a placebo-controlled phase 3 trial dubbed True North. In the study, researchers evaluated ozanimod as a single, daily oral therapy for both adults and pediatric patients at least 12 years old with moderately to severely active ulcerative colitis.

“Despite the availability of approved therapies, there is still unmet need and an opportunity to deliver additional treatment options to help patients better manage their disease,” said Adam Lenkowsky, general manager and head, U.S., Cardiovascular, Immunology and Oncology, Bristol Myers Squibb, in a statement. “We’re thrilled that our pursuit of transformative science in immunology may benefit patients in their ulcerative colitis treatment by introducing a new option that has a different mechanism of action than available therapies. Zeposia combines disease control through lasting remission and demonstrated safety in a once-daily pill.”

The Study

The study included more than more than 900 patients, at least 600 of which were dosed with ozanimod. A higher percentage of patients in the treatment arm (n = 429) experienced remission at week 10 (18.4% vs. 6.0%; P <0.0001) and maintained remission at a higher rate at week 52 (37.0% vs. 18.5%; P <0.0001).

The investigators also met secondary endpoints for clinical response and endoscopic improvement. Significantly more patients treated with ozanimod compared to placebo achieved clinical response at week 10 (47.8% vs. 25.9%; P <0.0001), endoscopic improvement (27% vs. 12%, P <0.0001), and endoscopic-histologic mucosal improvement (13% vs. 4%, P <0.001) at week 10.

During maintenance at week 52 (ozanimob n = 230 vs. placebo n = 227) the trial met its primary endpoint of clinical remission (37% vs. 19%, P <0.0001) as well as key secondary endpoints, including clinical response (60% vs, 41%, P <0.0001), endoscopic improvement (46% vs. 26%, P <0.001), corticosteroid-free clinical remission (32% vs. 17%, P <0.001), and endoscopic-histologic mucosal improvement (30% vs. 14%, P <0.001).

The researchers also observed decreases in rectal bleeding and stool frequency subscores as early as week 2 in the treatment arm.

The Drug

The mechanism in which the treatment exerts therapeutic effects in ulcerative colitis is not currently known, but it could involve the reduction of lymphocyte migration into the intestines.

By targeting S1P receptors on lymphocytes, a type of immune system cell, ozanimod reduces the number of lymphocytes in peripheral blood.

Safety

Ozanimob is contraindicated in patients who in the last six months experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure or have the presence of Mobitz type II second-degree or third degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker; patients with severe untreated sleep apnea; and patients taking a monoamine oxidase (MAO) inhibitor.

The most common adverse reactions with an incidence of at least 4% were liver test increased, upper respiratory infection, and headache.

Other Indications

There are also ongoing studies testing ozanimod for the treatment of Crohn’s disease.

Ozanimod was given FDA approval in 2020 for the treatment of adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS.